Abstract: :
Purpose:To analyze extremely discordant sibpairs to search forenvironmental and genetic factors that may contribute to thedevelopment of the neovascular form of age-related macular degeneration(AMD).Methods:We ascertain sibships in which one member hasthe neovascular form of AMD in at least one eye and an oldersibling has normal maculae or, at most, only a few drusen. Diseasestatus is confirmed by reading fundus photographs of every participantby at least two of the investigators. Clinical, dietary, andother factors are collected through interviews with the participants.Factors that are under scrutiny include gender, body weight,iris color, smoking history, multivitamin use, vitamin E use,aspirin use, alcohol consumption, and history of hypertension.The reference age for both the affected and unaffected siblingsin a pair was the time of diagnosis of AMD of the affected member.The McNemar test for correlated proportions was used to assessstatistical significance of possible risk factors for AMD. Bloodsamples are also collected for future molecular genetic approachesto search for genetic loci that may correlate with neovascularAMD.Results:So far, we have collected 42 extremely discordantsibpairs, and in 31 of these we have obtained complete epidemiologicaldata. Of these 31 pairs, 26 had an unaffected older siblingwith normal maculae and 5 had an unaffected older sibling withonly a few macular drusen. Preliminary analysis of these 31pairs revealed an association between smoking 25 or more pack-yearsof cigarettes and neovascular AMD, but this was only of borderlinestatistical significance (p = 0.013). No other statisticallysignificant association was found. We continue to recruit sibpairsand assess additional possible risk factors.Conclusion:Ourearly results are in accord with previous reports that smokingcigarettes correlates with the neovascular form of AMD. Otherfactors did not appear to be associated with AMD; however, someassociations might be missed in our currently small set of sibpairs.We believe that the extremely discordant sibpair method, whichto our knowledge has not previously been utilized to study thisdisease, is a powerful approach for elucidating epidemiologicaland genetic factors that contribute to neovascular AMD.